Microfibril Structure Masks Fibrillin-2 in Postnatal Tissues

被引:44
|
作者
Charbonneau, Noe L. [1 ]
Jordan, C. Diana [3 ]
Keene, Douglas R. [1 ]
Lee-Arteaga, Sui [4 ]
Dietz, Harry C. [5 ]
Rifkin, Daniel B. [6 ]
Ramirez, Francesco [4 ]
Sakai, Lynn Y. [1 ,2 ]
机构
[1] Shriners Hosp Children, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA
[3] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA
[4] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA
[5] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA
[6] NYU, Langone Med Ctr, Dept Cell Biol, New York, NY 10016 USA
基金
美国国家卫生研究院;
关键词
EXTRACELLULAR MICROFIBRILS; MARFAN-SYNDROME; EXPRESSION; ORGANIZATION; COMPONENT; DOMAIN; IDENTIFICATION; PROTEINS; BONE;
D O I
10.1074/jbc.M109.087031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fibrillin microfibrils are polymeric structures present in connective tissues. The importance of fibrillin microfibrils to connective tissue function has been demonstrated by the multiple genetic disorders caused by mutations in fibrillins and in microfibril-associated molecules. However, knowledge of microfibril structure is limited, largely due to their insolubility. Most previous studies have focused on how fibrillin-1 is organized within microfibril polymers. In this study, an immunochemical approach was used to circumvent the insolubility of microfibrils to determine the role of fibrillin-2 in postnatal microfibril structure. Results obtained from studies of wild type and fibrillin-1 null tissues, using monoclonal and polyclonal antibodies with defined epitopes, demonstrated that N-terminal fibrillin-2 epitopes are masked in postnatal microfibrils and can be revealed by enzymatic digestion or by genetic ablation of Fbn1. From these studies, we conclude that fetal fibrillin polymers form an inner core within postnatal microfibrils and that microfibril structure evolves as growth and development proceed into the postnatal period. Furthermore, documentation of a novel cryptic site present in EGF4 in fibrillin-1 underscores the molecular complexity and tissue-specific differences in microfibril structure.
引用
收藏
页码:20242 / 20251
页数:10
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